Oxygen-ozone Therapy Plus Antibiotic Therapy in the Treatment of Infections Secondary to Implant of Orthopaedic Devices

Not Applicable

Recruiting

• Conditions: Infection
• Interventions: Procedure: Oxygen-ozone therapy

• Registration Number: NCT04787575
• Lead Sponsor: Società Scientifica Internazionale di Ossigeno Ozono Terapia

Brief Summary

This is an open-label, multicentre, randomized, parallel group study to evaluate the efficacy of treatment with oxygen-ozone therapy plus oral antibiotic therapy, in comparison with oral antibiotic therapy alone, in the proportion of patients with resolution/improvement of signs and symptoms of infection of the wound (e.g. ulcer, eschar, sore) in the target lesion after 14 days of treatment, in patients with infections secondary to implant of orthopaedic devices.

Detailed Description

This will be an open-label, multicentre, randomized, parallel group study. The study plan will include a screening visit (Visit 1, Day -7/-3) in which patients will be screened on the basis of inclusion/exclusion criteria and clinically evaluated.

At the end of the 3-7 days of run-in (Visit 2, Baseline visit, Day 0), patient still eligible will be randomised to one of the two following treatment groups:

1. Oxygen-ozone therapy SIOOT plus antibiotic therapy

2. Antibiotic therapy

Patients in both groups will receive oral antibiotic therapy, which will be prescribed at discretion of the Investigator, based on the results of the colture of the swab collected in the target lesion at the screening visit (and later, if needed) and the associated antibiogram.

Follow-up visits will be performed after 7 days (Visit 3, Day 7), 14 days (Visit 4, Day 14), 28 days (Visit 5, Day 28) and 42 days (Visit 6, End of study, Day 42) from the start of treatment.

A visit window of ± 2 days for the date of Visits 3-5 and of ± 3 days for the date of Visits 6 will be allowed.

Patients prematurely discontinued from the study will perform an 'Early termination visit', in which procedures schedule for Visit 6 (End of study, Day 42) will be performed. In case of premature study discontinuation, the Investigator will duly record the reason for premature withdrawal in the appropriate section of the case report form (eCRF).

Visit 6, or the 'Early termination Visit' will represent the conclusion of patient's participation in the investigation.

Study Timeline

• Study First Submitted: 2021-02-18
• Study First Submitted QC: 2021-03-05
• Study First Posted: 2021-03-08
• Study Start: 2024-01-24
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-17
• Primary Completion: 2025-09
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1. Signed written informed consent;
2. Male or female aged ≥ 18 years;
3. Patient having undergone surgery for implant of an orthopaedic device in the previous 8 weeks;
4. Presence of at least one (but no more than 3) post-operative wounds in the site of surgery (ulcers, eschars, sores);
5. Presence of at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling, purulent secretion) of infection of at least moderate intensity (score ≥ 2) in the target lesion at the screening visit (Visit 1), to be confirmed again at the baseline visit (Visit 2);
6. Wound area of the target lesion ≤ 100 cm2;
7. Patient with presence at least one pathogen identified in the swab collection in the target lesion, which is amenable to be eradicated with oral antibiotic therapy;
8. In case of multiple wounds (however not more than three), non-target lesions must not overlap with the target one (i.e. the largest one);
9. Patient able to perform the wound self-care at home or care by his/her primary caregiver;
10. Willing to refrain from all non-permitted concomitant medication from the screening visit through to the entire study duration.
11. Female subjects of childbearing potential must have a negative urinary pregnancy test at Screening and must practice a reliable method of contraception throughout the study;
12. Patient able to read and understand the study procedures, the requirements for follow-up visits, willing to provide information at the scheduled evaluations and willing, able and ensuring to comply with the study requirements for the whole study period.

Exclusion Criteria

1. Wounds without signs of localized infection;
2. Presence of more than four wounds;
3. Presence of one or more wounds with area > 100 cm2;
4. Presence of undermining wounds;
5. Patients with favism, i.e. deficiency of the glucose-6-phosphate dehydrogenase (G6PD) enzyme;
6. Patients with uncontrolled hyperthyroidism;
7. Patients with history of connective tissue disease, e.g., mixed connective tissue disease;
8. Patients with active malignant disease;
9. Patients with other clinically significant diseases, or other major diseases deemed clinically significant by the Investigator or which in the opinion of the Investigator would interfere with the study procedures or study outcome;
10. Patients candidate to any surgery during the overall study duration;
11. Treatment with topical corticosteroids in the previous 4 weeks and/or with systemic corticosteroids in the previous 7 days;
12. Treatment with any hydrating and/or moisturizing cream in the previous 24 hours.
13. Patients on treatment with chemotherapeutic agents, radiation therapy or immunosuppressive therapies;
14. Patients with contraindications to antibiotic therapy;
15. Pregnant, breastfeeding women and female child-bearing potential who are not using a highly effective method of birth control and not willing to use it during the participation to the study;
16. Participation in any clinical research study evaluating another investigational drug or device within 30 days prior to consenting to study entry;
17. Patient unable to understand informed consent or having a high probability of non-compliance with the study procedures and or non-completion of the study according to investigator's judgement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Oxygen-ozone therapy	Oxygen-ozone therapy plus antibiotic therapy
Arm B	Oxygen-ozone therapy	Antibiotic therapy

Primary Outcome Measures

Name	Time	Method
Clinical success at Day 14	2 week	Resolution/improvement of signs and symptoms of infection of the wound in the target lesion (i.e. a score ≤ 1 for a maximum of two signs/symptoms) from baseline to Day 14. The following symptoms will be evaluated by patients on a 0-4 point Likert scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom; 4 = very severe symptom): pain, burning, redness and malodour.; The following signs will be evaluated by investigators on a 0-4 point Likert scale (0 = no sign; 1 = mild sign; 2 = moderate sign; 3 = severe sign; 4 = very severe sign): erythema, local warmth, swelling, purulent secretion.

Secondary Outcome Measures

Name	Time	Method
Changes in High-sensitivity C-reactive protein	7 weeks	Changes from baseline to Day 14 (V4) and Day 42 (V6) of hs-CRP values (a laboratory parameters that is indicative of infection)
Eradication of the pathogen isolated at the screening visit	7 weeks	Bacteriological success of the wound in the target lesion at Day 14 (V4) and Day 42 (V6).A bacteriological success is defined as eradication of the pathogen isolated at the screening visit, without superinfection or reinfection with the same pathogen;
Global assessment of the target lesion at Day 14 and Day 42	7 weeks	Investigators will be requested to score the outcome of the target lesion on a five-grade scale: 1= worsening, 2 = no change, 3 = minimal improvement, 4 = moderate improvement and 5 = good improvement/resolution;
Changes in WBCs count	7 weeks	Changes from baseline to Day 14 (V4) and Day 42 (V6) of white blood cells count (a laboratory parameters that is indicative of infection)
Changes in Erythrocyte sedimentation rate	7 weeks	Changes from baseline to Day 14 (V4) and Day 42 (V6) of ESR values (a laboratory parameters that is indicative of infection)
Proportion of patients with clinical success at Day 7, Day 28, and Day 42	Day 7, Day 28, and Day 42	Clinical success is defined as resolution/improvement of signs and symptoms of infection of the wound in the target lesion
Time to resolution of all signs and symptoms of infection	7 weeks	It is defined as the disappearance (score = 0) of all signs and symptoms of infection of the wound in the target lesion;
Changes from baseline to any post-baseline time-point in body temperature	7 weeks
Changes from baseline to any post-baseline time-point of the size of the target lesion	7 weeks

Trial Locations

Locations (6)

Pineta Grande Hospital; 🇮🇹 Castel Volturno, Caserta, Italy

Ospedali Riuniti Torrette; 🇮🇹 Ancona, Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone di Palermo; 🇮🇹 Palermo, Italy

Università Federico II; 🇮🇹 Napoli, Italy

Casa Di Cura Citta' Di Roma; 🇮🇹 Roma, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy